Fig. 4

Metabolic interactions between tumor cells and GAMs. Tumor cells cause massive accumulation of lactate in the TME via the Warburg effect, and lactate further induces macrophages to express VEGF and Arg1 via the HIF1α signaling pathway, which promotes polarization of macrophages toward M2 phenotype. Adenosine produced by tumor cell metabolism can also promote M2-type polarization in macrophages. Macrophages release IL‐1β, which triggers phosphorylation of GPD2 at T10 via PKCδ, to promote glycolysis in glioma cells. Macrophages produce IL-6, which induces PDPK1-dependent PGK1 T243 phosphorylation to promote glycolysis in glioma cells. PDPK1, 3-phosphoinositide-dependent protein kinase 1; PGK1, phosphoglycerate kinase 1; PKCδ, protein kinase-delta; GPD2, glycerol‐3‐phosphate dehydrogenase; IL-1β, interleukin-1β; IL-6, interleukin-6; HIF1α, hypoxia inducible factor 1 alpha; MCT1-4, monocarboxylate transporter1-4; VEGF, vascular endothelial growth factor; Arg1, arginase 1